title: Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-κB.
abstract: Immune cell infiltration of expanding adipose tissue during obesity and its role in insulin resistance has been described and involves chemokines. However, studies so far have focused on a single chemokine or its receptor (especially CCL2 and CCL5) whereas redundant functions of chemokines have been described. The objective of this work was to explore the expression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-α) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expression was investigated in human subcutaneous adipose tissue biopsies and mechanism of chemokine expression was investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the most responsive genes in TNF-α treated human and mouse adipocytes. mRNA and protein of 34 chemokine genes were induced in a dose-dependent manner in the culture system. Furthermore, expression of those chemokines was elevated in human obese adipose tissue. Finally, chemokine expression was reduced by NF-κB inactivation and elevated by NF-κB activation. Our data indicate that besides CCL2 and CCL5, numerous other chemokines such as CCL19 are expressed by adipocytes under obesity-associated chronic inflammation. Their expression is regulated predominantly by NF-κB. Those chemokines could be involved in the initiation of infiltration of leukocytes into obese adipose tissue.
authors.affiliation: INRA, UMR 1260, Marseille, France ; INSERM, UMR 1062, « Nutrition, Obésité et Risque Thrombotique », Marseille, France ; Université d'Aix-Marseille, Faculté de Médecine, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Tourniaire
authors.forename: Beatrice
authors.initials: B
authors.lastname: Romier-Crouzet
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Julie
authors.initials: J
authors.lastname: Marcotorchino
authors.forename: Erwan
authors.initials: E
authors.lastname: Gouranton
authors.forename: Jerome
authors.initials: J
authors.lastname: Salles
authors.forename: Christiane
authors.initials: C
authors.lastname: Malezet
authors.forename: Julien
authors.initials: J
authors.lastname: Astier
authors.forename: Patrice
authors.initials: P
authors.lastname: Darmon
authors.forename: Eric
authors.initials: E
authors.lastname: Blouin
authors.forename: Stephane
authors.initials: S
authors.lastname: Walrand
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Landrier
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha